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Updated: Jul 13, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Induction of renal endonuclease G by cisplatin is reduced in DNase I-deficient mice
Xiaoyan Yin1, Eugene O Apostolov, Sudhir V Shah
1Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Abstract:
Nephrotoxicity from the chemotherapeutic drug cisplatin is associated with DNA fragmentation and cell death. We have recently demonstrated that DNase I knockout mice are significantly protected against cisplatin nephrotoxicity, but it is unknown whether the DNA fragmentation that occurs is produced by DNase I or another endonuclease. In this study we assessed the expression of several endonucleases involved in cell death after injection of cisplatin and found that the expression of endonuclease G (EndoG) increased whereas the expression of DNase I decreased almost to zero. Immunostaining showed that some nuclei contained both fragmented DNA and EndoG, suggesting that EndoG may cause DNA fragmentation induced by cisplatin. The increase in expression of EndoG was greater in wild-type mice than in DNase I knockout mice, indicating a potential link between the two endonucleases. In support of such a link, overexpression of DNase I in cultured mouse tubular epithelial cells also induced EndoG. Furthermore, gene silencing of EndoG in vitro provided significant protection against cell death. Taken together, our data suggest that both DNase I and EndoG mediate cisplatin injury to tubular epithelial cells.
Insights
Cisplatin chemotherapy causes kidney damage via DNA fragmentation. This study reveals that both DNase I and endonuclease G (EndoG) contribute to this DNA damage and cell death in kidney cells.
Area of Science:
- Nephrology
- Molecular Biology
- Oncology
Background:
- Cisplatin chemotherapy can cause significant nephrotoxicity.
- DNA fragmentation and cell death are hallmarks of cisplatin-induced kidney injury.
Purpose of the Study:
- To investigate the roles of specific endonucleases, DNase I and endonuclease G (EndoG), in cisplatin nephrotoxicity.
- To determine whether EndoG contributes to DNA fragmentation observed after cisplatin treatment.
Main Methods:
- Assessed endonuclease expression in mice after cisplatin injection.
- Utilized immunostaining to localize endonucleases and DNA fragmentation within kidney cells.
- Examined the effects of DNase I overexpression and EndoG gene silencing in cultured kidney cells.
Main Results:
- Cisplatin treatment increased endonuclease G (EndoG) expression while decreasing DNase I expression.
- Immunostaining indicated EndoG co-localization with fragmented DNA in nuclei, suggesting its role in DNA fragmentation.
- Overexpression of DNase I induced EndoG, and gene silencing of EndoG protected cells from cisplatin-induced death.
Conclusions:
- Both DNase I and EndoG play a role in mediating cisplatin-induced injury to kidney tubular epithelial cells.
- Endonuclease G appears to be a key mediator of DNA fragmentation and cell death following cisplatin exposure.
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